PB2339: CLINICAL OUTCOMES OF RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: THE ROLE OF AUTOLOGOUS STEM-CELL TRANSPLANTATION IN AN INTEND TO TREAT POPULATION
Authors: Isabel Paulos Mesquita, Margarida Duarte, Eduardo Espada, Daniela Alves, Joao Forjaz de Lacerda, João Raposo
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Diffuse large B-cell lymphoma (DLBCL) has a high cure rate. However, a considerable number of patients experience relapse or refractoriness (R/R) to first-line therapy. The current standard of care for eligible patients consists of salvage chemotherapy followed by autologous stem-cell transplantation (ASCT). Aims: Analysis of the baseline clinical characteristics, predictors of response to the standard salvage regimens and ASCT and survival outcomes in patients with R/R DLBCL. Methods: Retrospective observational single-centre study involving transplant-eligible patients (pts) with R/R DLBCL, who have started salvage therapy (ST) between 2016 and 2021. Refractory disease was defined as unresponsive/progressive disease within the 6-month period following the start of the last cycle of ST. Bulky disease was defined as a mass greater than 10cm in one axis. Clinical data were obtained by review of electronic medical records. Results: Our cohort included 31 pts, 54.8% male, with a median age at diagnosis of 58 years (interquartile range [IQR] 48-64). 89.7% were treated with R-CHOP at frontline (1LT), with a median time from diagnosis to disease progression (DP) of 24 months (mo) (IQR 9.8-42.9). 62.1% were considered refractory to 1LT. Salvage regimens included R-ICE (41.9%) (gr1), R-ESHAP (35.5%) (gr2) and R-GEMOX (16.1%) (gr3), with no differences in the baseline characteristics between groups. Consolidation with ASCT was performed in 32.3% of pts, half of whom remained alive at data collection time. Overall response rate (ORR) of ST was 33.3%, with no difference in response rates between groups (p=0.749; R-ICE vs. R-ESHAP p=0.534). However, only 3 pts from gr2 reached ASCT, as opposed to 6 pts from gr1 (80% of which showed CR after ASCT vs. 0% in gr2). Overall death rate was 77.4%: 58.3% due to DP and 33.3% due to treatment-related toxicities. There were less deaths within gr1 (53.8% vs. 100% in gr2 and gr3; p=0.010) and the group of pts submitted to ASCT (50.0% vs. 90.5%; p=0.022). Median overall survival (OS) was 22.5mo from diagnosis and 10.2mo from the start of ST. Longer OS was observed within patients with lower-stage disease at diagnosis, absence of bulky disease and responsive disease to 1LT. The use of R-ICE as ST was associated with better OS from the start of ST (16.3mo vs. 5.5mo in gr2; p=0.028) (Fig1). ASCT was also associated with better OS from ST (28.3 vs. 7.7mo; p=0.008) (Fig2). Median progression-free survival (PFS) was 2.9mo from ST and 14.7mo from ASCT, with no difference between salvage regimens (p=0.602). ASCT did not have impact on PFS either (p=0.327), although after ASCT there was a trend towards better PFS in gr1 (vs. gr2; p=0.066) (Fig3). In univariate Cox-regression analysis, the use of ASCT (HR 0.097; 95% CI 0.019-0.490; p=0.005) and R-ICE as ST (vs. R-ESHAP: HR 0.293; 95% CI 0.103-0.832; p=0.021) both appeared beneficial regarding OS from ST. This effect was retained in multivariate analysis for both variables, with ASCT showing a higher protective effect (HR 0.097 vs. 0.293). There was no significant effect on PFS for either variable. Summary/Conclusion: Although ASCT has demonstrated a beneficial effect in this cohort, only a limited number of patients have shown chemosensitivity, and many died from therapy-related complications. Our results underline the strong need for better treatment options in this setting, reflecting the current shift towards a new standard of care in the age of cellular therapies and bispecific antibodies.Keywords: Salvage chemotherapy, Diffuse large B cell lymphoma, Autologous hematopoietic stem cell transplantation